The general goal of this project is to delineate the mechanisms involved in the regulation of the activation of thymus-dependent (T) and thymus-independent (B) lymphocytes. To this end, studies of the genetic regulation of T lymphocyte activation directed at an analysis of the role of molecules encoded in the major histocompatibility complex (MHC) have been carried out. These experiments strongly suggest that T lymphocytes possess antigen-binding receptors which recognize complex antigenic determinants involving both conventional antigen and an MHC structure expressed on an auxilliary cell. The other principal approach has been to analyze the requirements for B lymphocyte activation by studying the responses and surface markers of B lymphocytes derived from a strain of mice with an X-linked defect in B lymphocyte maturation or function.